Swift Luther M, Jaimes Rafael, McCullough Damon, Burke Morgan, Reilly Marissa, Maeda Takuya, Zhang Hanyu, Ishibashi Nobuyuki, Rogers Jack M, Posnack Nikki Gillum
Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital; Children's National Heart Institute, Children's National Hospital.
Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital; Children's National Heart Institute, Children's National Hospital; Center for Neuroscience Research, Children's National Hospital.
J Vis Exp. 2019 Nov 7(153). doi: 10.3791/60472.
Small animal models are most commonly used in cardiovascular research due to the availability of genetically modified species and lower cost compared to larger animals. Yet, larger mammals are better suited for translational research questions related to normal cardiac physiology, pathophysiology, and preclinical testing of therapeutic agents. To overcome the technical barriers associated with employing a larger animal model in cardiac research, we describe an approach to measure physiological parameters in an isolated, Langendorff-perfused piglet heart. This approach combines two powerful experimental tools to evaluate the state of the heart: electrophysiology (EP) study and simultaneous optical mapping of transmembrane voltage and intracellular calcium using parameter sensitive dyes (RH237, Rhod2-AM). The described methodologies are well suited for translational studies investigating the cardiac conduction system, alterations in action potential morphology, calcium handling, excitation-contraction coupling and the incidence of cardiac alternans or arrhythmias.
由于基因改造物种的可得性以及与大型动物相比成本较低，小动物模型在心血管研究中最为常用。然而，大型哺乳动物更适合用于与正常心脏生理学、病理生理学以及治疗药物临床前测试相关的转化研究问题。为了克服在心脏研究中使用大型动物模型所带来的技术障碍，我们描述了一种在离体的、Langendorff灌注的仔猪心脏中测量生理参数的方法。这种方法结合了两种强大的实验工具来评估心脏状态：电生理学（EP）研究以及使用参数敏感染料（RH237、Rhod2-AM）对跨膜电压和细胞内钙进行同步光学映射。所描述的方法非常适合用于研究心脏传导系统、动作电位形态改变、钙处理、兴奋-收缩偶联以及心脏交替或心律失常发生率的转化研究。
